Obesity is a critical health problem for U.S. minority populations, 60-70% of whom are either overweight or obese. This is particularly alarming because by 2050 Latinos and African-Americans will constitute nearly 50% of the U.S. population. Given these data, it is imperative that more research be done to understand the predictors of and mechanisms contributing to obesity and its effects on health outcomes in African Americans and Hispanics. Cross-sectional studies have revealed strong associations between abdominal obesity, specifically visceral adipose tissue (VAT) and cardio-metabolic conditions such as hypertension, inflammation and insulin resistance. Adverse lifestyle factors including diet, smoking, and inactivity - are associated with increased VAT and cardio-metabolic disease. However, few studies have examined the role of change in VAT on cardio-metabolic risk factors, particularly in minority populations. Moving our understanding from mere cross sectional associations between lifestyle, VAT and CVD to the causal relationships that connect the lifestyle to CVD will be vital for developing the rationale for future interventional studies, particularly in high risk populations. In response to PA 09-133 (Secondary Analyses in Obesity, Diabetes and Digestive and Kidney Diseases), we propose to explore innovative, longitudinal hypotheses through the use of existing data sets and new laboratory assays of stored specimens in an NIH-supported longitudinal multi-ethnic cohort study, the IRAS Family Study (R01 HL060944). Our broad research hypothesis is that the accumulation of VAT is the link between adverse health behaviors and cardiometabolic risk. Specific aims are (1) to determine the relationship between 5-year change in VAT with 5-year change in cardiometabolic risk factors in African- Americans (N=369) and Hispanic-Americans (N=871), aged 18-60 years and (2) to determine if associations between lifestyle factors and cardiometabolic risk factors are mediated by change in VAT. The IRAS Family Study cohort is extensively characterized with regard to longitudinal changes in VAT, cardio-metabolic risk factors (blood pressure, insulin sensitivity, fasting serum lipids, PAI-1), and health behaviors (diet, sleep duration, smoking, physical activity). New assays of CRP, IL-6 and adiponectin will be conducted in stored specimens to obtain longitudinal measures of these biomarkers. The IRAS Family Study is ideally suited to answer these questions due to the large population of African-Americans and Hispanic-Americans with 5-year change in CT-derived fat measures and cardio-metabolic risk factors. Analytic strategies include innovative longitudinal analyses and mixed model approaches. Accumulation of VAT may be a predictor of adverse changes in cardio-metabolic risk factors, and may partially explain the observed association between adverse health behaviors and cardiometabolic factors. If this hypothesis is supported, our project would provide important information to guide clinical trials of lifestyle interventions specifically targting weight loss in the visceral depots, explicitly to reduce risk of cardiovascular and metabolic diseases.